Sustained or controlled release formulations that provide for continued release of orally administered pharmaceuticals. In the prior art these formulations have been based on coatings that are gradually eroded or dissolved. In addition, it is known to use discrete polymeric units that have been impregnated with a drug that will be slowly leached from the polymeric unit by the action of gastro intestinal fluids. In order to prepare sustained or controlled release formulations of 1,4-dihydropyridine, it is important that the drug is adequately soluble in water or in a pharmaceutically acceptable solvent in order to achieve therapeutic blood levels. It is also important that the solubility characteristics be substantially unaffected by environmental conditions (heat, light, moisture) or by the manufacturing process that is employed to make the sustained or controlled release composition. PCT application WO 83/2230 (CA 102(8) 154832) discloses dry capsules that were prepared with nifedipine, sucrose stearate, Pluronic F 68, lactose and methyl cellulose. CA 99(4): 27904d discloses a solidified melt of griseofulvin-Pluronic F 68 that shows increased bioavailability as compared to micronized griseofulvin.
The applicants have discovered that the solubility of the poorly soluble 1,4-dihydropyridines such as nilvadipine and nifedipine may be modified by forming a complex of said 1,4-dihydropyridines with a polyoxypropylene-polyoxyethylene block copolymer. These complexes have sufficient water solubility for use in the preparation of a sustained or controlled release pharmaceutical composition.
These complexes are stable over a wide temperture range and exhibit higher bioabsorbtion than presently available systems.